Learn more about Vitamin E Deficiency

Biochemical aspects of neurological disease

Paul Hart, ... Min Htut, in Clinical Biochemistry: Metabolic and Clinical Aspects (Third Edition), 2014

Vitamin E deficiency

Vitamin E deficiency only rarely causes an isolated neuropathy; measuring plasma vitamin E concentrations should not be part of the routine screen in neuropathy. Chronic vitamin E deficiency in developed countries is usually associated with disorders of lipid absorption. Vitamin E has a role in maintaining cell membrane structure and as a free radical scavenger. After long exposure to low concentrations of vitamin E, ataxia and axonal neuropathy may develop. The neurological features can improve with oral vitamin E treatment and it is also recommended that high doses of vitamin A should be given at the same time.

Clinical and Pathological Features of Hereditary Ataxiasemsp;

TETSUO ASHIZAWA, S.H. SUBRAMONY, in Animal Models of Movement Disorders, 2005

B. Ataxia with Vitamin E Deficiency (AVED)

Vitamin E deficiency may be presented with a phenotype that closely resembles FRDA. Patients with a previous diagnosis of FRDA and a negative genetic test for FRDA should be tested for serum vitamin E levels, which are very low (<5 μg/ml) in this disease. Although several diseases are known to lead to secondary vitamin E deficiency, mutations in the TTP1 gene (Ouahchi et al., 1995) on chromosome 8q13, encoding the α-tocopherol transfer protein, (Catignani et al., 1977) are the disease-causing mutations in autosomal recessive ataxia with primary vitamin E deficiency. Early onset and severe forms of the disease are caused by truncating or missense mutations in well-conserved amino acids (Cavalier et al., 1998). Early replacement therapy may prevent progression of the disease (Jackson et al., 1996; Schuelke et al., 1999).

Blindness, Anisocoria, and Abnormal Eye Movements

Michael D. Lorenz BS, DVM, DACVIM, ... Marc Kent DVM, BA, DACVIM, in Handbook of Veterinary Neurology (Fifth Edition), 2011

Vitamin E Deficiency

Vitamin E deficiency results in retinal degeneration and lipopigment accumulation beginning in the central area of the tapetum lucidum and progressing peripherally and is related to the role of vitamin E as an antioxidant. Regardless of the species, funduscopic examination reveals central retinal degeneration and patchy brown pigmentation of the retina (lipofuscin accumulation). Experimentally, vitamin E deficiency consistently results in visual defects in dogs.42 Naturally occurring hypovitaminosis E has been reported in a group of hunting dogs fed a deficient diet.43 Retinal pigment epithelial dystrophy (RPED) has been reported in a number of breeds of dog including the English cocker and Briard.44,45 Funduscopic examination is identical to dogs with vitamin E deficiency. Although not fully understood, dogs with RPED have abnormally low serum vitamin E levels unrelated to diet or malabsorption.46 Similarly, approximately 40% of horses with equine motor neuron disease, a disorder likely related to abnormal antioxidant properties possibly due to abnormal vitamin E metabolism, have observable lipofuscin accumulation in the retina despite rare visual deficits (see Chapter 7).47

Vitamin E

Larry R. Engelking, in Textbook of Veterinary Physiological Chemistry (Third Edition), 2015

Vitamin E Deficiency

Vitamin E deficiency can result from severe fat malabsorption with consequent steatorrhea, some forms of cholestatic liver disease, abetalipoproteinemia, and intestinal resection. In experimental animals vitamin E deficiency has resulted in fetal resorption, premature infants have been born with inadequate reserves, and in males testicular atrophy has occurred.

Excessive lipid peroxidation of membranes and other sites of fat accumulation accounts for most of the symptoms associated with vitamin E deficiency. The most clear-cut example is enhanced erythrocyte fragility, where RBCs exhibit a marked change in morphology and become easily destroyed. Vitamin E is also essential for the development and maintenance of normal nerve and muscle cell activity. Either vitamin E or selenium deficiency can result in a massive influx of Ca++ into cells; mitochondria become loaded with this element, and reduce their ATP output. This mineral influx results in muscular degeneration, and gives muscle a characteristic appearance (i.e., “white muscle disease”), which is usually more prominent in young animals. Myocardial involvement with this disease may result in sudden death.

White muscle disease is sometimes confused with the muscular dystrophies of animals, which are hereditary degenerative diseases of skeletal muscle. Dystrophic muscles usually contain fewer fibers, an increase in the number and size of nuclei, and myofibrillar degeneration without effective regeneration.

Another outcome of the lack of antioxidant action of vitamin E, and which occurs in its deficiency, is the accumulation of “lipofuscin” or “ceroid pigment” granules in many tissues, including the CNS, lungs, kidneys, adipocytes, and muscle. These granules contain oxidized unmetabolizable lipids that have partially crosslinked with protein or peptides to form a hard globule that cannot be disposed of by the organism. These granules normally accumulate with age, and this accumulation is inhibited by a high vitamin E intake, at least in mice. Fatty tissue inflammation (i.e., “steatitis”), is also associated with vitamin E deficiency.

Animals with cholestasis (e.g., bile duct obstruction) absorb fat-soluble vitamins poorly. In chronic conditions neuromuscular damage occurs that can be somewhat alleviated through parenteral administration of vitamin E. Additionally, retinopathy can occur in vitamin E deficiency upon exposure to high oxygen tensions. Again, this condition has been reversed with vitamin E administration.

Studies in several animal species have shown that in males, vitamin E deficiency results first in sperm immotility, then in degeneration of the seminiferous epithelium, and then cessation of sperm production. In females there is a failure of uterine function in vitamin E deficiency, with a lack of development of the vasculature that would allow the conceptus to implant in the uterine wall. Although vitamin E supplementation can help to reverse these symptoms, Se does not effectively prevent fetal resorption in rats, nor encephalomalacia in chickens, and thus, is not a complete substitute for vitamin E.

Although several health problems have been associated with vitamin E deficiency, as discussed above, high intakes of this vitamin do not appear to be as debilitating as do those for vitamins A, D and K. Vitamin E, however, can act as an anticoagulant, therefore hypervitaminosis E may increase the risk of bleeding.

Vitamins and the Immune System

Didem Pekmezci, in Vitamins & Hormones, 2011

III Vitamin E Deficiency

Vitamin E deficiency was first described by Evans and Bishop in 1922 in experimental animals, when it was discovered to be essential for fertility. While vitamin E deficiency is rare in well-nourished healthy subjects (Wu et al., 2006), it is not a problem even among people living on relatively poor diets (Bender, 2003). It was not until 1983 that vitamin E was demonstrated to be a dietary essential for human beings, when Muller et al. (1983) described the devastating neurological damage from lack of vitamin E in patients with hereditary abetalipoproteinemia. Indeed, vitamin E deficiency could be classified in two classes in human beings. One of them is physiologically occurs and includes: the pregnancy and neonatal periods, and the second one is generally can be caused by genetic defects. Vitamin E is extremely important during the early stages of life, from the time of conception to the postnatal development of the infant (Debier, 2007). Several key stages such as fertilization, development of early embryos (blastocyst stage), implantation, and placental maturation have been identified for vitamin E needs (Ashworth and Antipatis, 2001; Jishage et al., 2001, 2005; Kaempf-Rotzoll et al., 2002; Wang et al., 2002). Vitamin E is also an essential molecule to protect the fetus from an irreparable oxidative stress (Jishage et al., 2001; Kaempf-Rotzoll et al., 2002). Finally, at birth, an adequate supply of vitamin E to the newborn is of utmost importance to protect the organism against oxygen toxicity and to stimulate the development of its immune system (Babinszky et al., 1991; Ostrea et al., 1986), and obviously seen that newborn or premature infants seem particularly susceptible to vitamin E deficiency, while a wide variety of disorders benefit from supplementation (Oski, 1980; Scott, 1980). However, Vitamin E deficiency in human beings is almost always due to factors other than dietary insufficiency (Eitenmiller and Lee, 2004). Deficiency results from genetic abnormalities in production of the α-TTP, fat malabsorption syndromes, and protein-energy malnutrition (Food and Nutrition Board, and Institute of Medicine, 2000). Patients with congenital abetalipoproteinemia, who are unable to synthesize VLDL, were the first condition reported that confirmed the essentiality of vitamin E in human beings (Muller et al., 1983). Genetic abnormalities in lipoprotein metabolism can produce low levels of chylomicrons, VLDLs, and low-density lipoprotein (LDL) that affect absorption and transport of vitamin E (Rader and Brewer, 1993). Abetalipoproteinemia is an autosomal recessive genetic disorder that leads to mutations in the microsomal triglyceride transfer protein (Gordon, 2001; Rader and Brewer, 1993; Wetterau et al., 1991). The microsomal triglyceride transfer protein is completely absent from the intestines of abetalipoproteinemia patients (Wetterau et al., 1992). Patients that have undetectably low plasma levels of α-tocopherol develop devastating ataxic neuropathy and pigmentary retinopathy (Bender, 2003). [email protected];s ataxia is an autosomal recessive disease characterized by cerebellar ataxia, dysarthria, sensory loss in the lower limbs, and other neurological symptoms (Ben Hamida et al., 1993; Stumpf et al., 1987). Early studies on [email protected];s ataxia identified a variant form characterized by normal fat absorption and very low levels of plasma vitamin E. Neurological symptoms were considered to be due to vitamin E deficiency (Ben Hamida et al., 1993; Stumpf et al., 1987). Humans with a defective α-TTP gene have also severe vitamin E deficiency (Cavalier et al., 1998; Ouahchi et al., 1995) with extremely low plasma, nerve, and adipose tissue α-tocopherol concentrations (Traber et al., 1987). Patients who lack the hepatic tocopherol transfer protein and suffer from what has been called ataxia with vitamin E deficiency (AVED) are unable to export α-tocopherol from the liver in VLDL (Bender, 2003; Ouahchi et al., 1995), and display autosomal recessive inheritance of progressive neurodegenerative symptoms (e.g., ataxia, dysarthria, loss of deep tendon reflexes), coupled with low plasma vitamin E levels (≤ 3 μM) (Manor and Morley, 2007). Plasma and tissue levels of other lipids (e.g., cholesterol, triglycerides) are typically unaffected (Manor and Morley, 2007). When deficiency does occur, the cause is usually malabsorption as a result of fat malabsorption or genetic abnormalities in lipoprotein metabolism (Meydani and Beharka, 1998). Therefore, few studies have directly examined the effect of vitamin E deficiency on immunologic parameters in adult humans. Deficiencies in vitamin E have also been reported in Human Immunodeficiency Virus (HIV)-infected individuals (Meydani and Beharka, 1998). Plasma vitamin E levels were detected significantly lower in a study of 200 HIV-positive individuals compared with controls (Passi et al., 1993), and these deficiencies were not appear to be due to inadequate intake of vitamin. Favier et al. (1994) observed that patients, who had already developed Acquired Immune Deficiency Syndrome (AIDS), had an inverse relationship between serum vitamin E levels and severity of disease. Vitamin E deficiency, in turn, exacerbates the immune dysfunctions caused by HIV infection, leaving individuals more susceptible to opportunistic infections (Tang and Smit, 1998). Vitamin E deficiency in experimental animals results in a number of different conditions, with considerable differences between different species in their susceptibility to different signs of deficiency (Bender, 2003). Results from animal and human studies indicate that vitamin E deficiency impairs both humoral and cellular immunity (Gebremichael et al., 1984; Kowdley et al., 1992). In addition, Bendich (1988) has also reported that both T- and B-cell functions were impaired by vitamin E deficiency. Vitamin E deficiency and the immune response in several studies are presented in Table 8.1.

Table 8.1. Vitamin E deficiency and the immune response

Research speciesImmune responseReferences
Mice↓Plaque-forming cells (PFC), ↓hemagglutination (HA) titerTengerdy et al. (1973)
Pigs↓Lymphocyte proliferation (Con A, PHA)Teige et al. (1978)
Dogs↓Lymphocyte proliferation (Con A, PHA, PWM)Sheffy and Schultz (1979)
Mice↓Lymphocyte proliferation (Con A, PHA, LPS)Corwin and Shloss (1980)
Rats↓ Chemotactic and phagocytic stimuli of PMNHarris et al. (1980)
Dogs↓Lymphocyte proliferation (Con A, PHA, PWM)Langweiler et al. (1981)
Calves↔Total IgG1, IgG2, IgMCipriano et al. (1982)
Mice↓Lymphocyte proliferation (Con A, PHA)Corwin and Gordon (1982)
Rats↓M histocompatibilityGebremichael et al. (1984)
Mice↓T-cell activitySharp and Colston (1984)
Rats↓Lymphocyte proliferationEskew et al. (1986)
Pigs↓Lymphocyte proliferation (Con A, PHA)Jensen et al. (1988)
Rats↓Cellular immunityMoriguchi et al. (1989)
Lambs↓Lymphocyte proliferationTurner and Finch (1990)
Human↓Lymphocyte proliferation (Con A, PHA), ↓DTH, ↓IL-2Kowdley et al. (1992)
Sow↓Peripheral blood lymphocytes, ↓Polymorphonuclear cell (PMN)Wuryastuti et al. (1993)
Chickens↓Lymphocyte proliferation (Con A, PHA)Chang et al. (1994)

Concanavalin A (Con A), Phytohaemagglutinin (PHA), Pokeweed mitogen (PWM), Lipopolysaccharides (LPS), Polymorph nuclear neutrophils (PMN), Delayed-type hypersensitivity (DTH).

Alcohol

H.K. Seitz, S. Mueller, in Reference Module in Biomedical Sciences, 2014

Vitamin E

Vitamin E deficiency in the alcoholics is explained by an increased degradation as well as a shift of the distribution of isomers of vitamin E in the liver. Vitamin E is a vitamin complex with its most important representative α-tocopherol, γ- and δ-tocopherol are also important, but less biological active as compared to α-tocopherol. Chronic alcohol consumption causes a shift from α- to γ-tocopherol with a loss of α-tocopherol in the liver and other organs which enhances vitamin E deficiency (Meydani et al., 1991). Since tocopherols produce a complex with unsaturated fatty acids in membranes, they protect against lipid peroxidation by ROS. Since alcohol metabolism leads to an increase in ROS, an adequate vitamin E level is of major importance to neutralize ROS. In animal experiments it seems that the additional administration of vitamin E decreases alcohol associated cellular hyperproliferation in the colon (Vincon et al., 2003).

Advances in Cellular Neurobiology

C.L. Dolman, P.M. MacLeod, in Advances in Cellular Neurobiology, 1981

A Brown Bowel Syndrome

Vitamin E deficiency induced in animals leads to brown pigmentation of the smooth muscle of uterus and gastrointestinal tract (Fisher, 1969). This is suspected to be the cause of the “brown bowel syndrome,” an intense brown discoloration of the tunica propria of the gastrointestinal tract, first observed over 100 years ago (Wagner, 1861), and found primarily in malabsorption but also in chronic hepatic disorders (Pappenheimer and Victor, 1946; Foster, 1979; Hitzman et al., 1979). The brown color results from heavy lipofuscin or ceroid deposition in the smooth musculature. The lack of vitamin E, an antioxidant and membrane stabilizer, leads to degradation of membranes, particularly mitochondria (Foster, 1979), and peroxidation and polymerization of unsaturated fatty acids to chromolipids (Casselman, 1951).

Vitamin deficiencies

E.M.E. Poskitt MA, MB, BChir, FRCP, in Practical Paediatric Nutrition, 1988

Vitamin E deficiency

Neonatal vitamin E deficiency has been discussed in Chapters 4 and 5. In older children vitamin E deficiency has only been shown recently to have clinical manifestations (Harding et al., 1982). In abetalipoproteinaemia (see Chapter 15) correction of low circulating levels of vitamin E modifies or prevents the development of neurological signs of the later stages of the condition (Muller, Lloyd and Bird, 1977). Children with abetalipoproteinaemia have steatorrhoea. Since vitamin E is a fat-soluble vitamin, malabsorption is likely.

More recently, some older children and adults with cystic fibrosis have developed neurological signs similar to those that develop in abetalipoproteinaemia (Bye et al., 1985). It is now felt advisable for children with cystic fibrosis and other fat malabsorption syndromes to receive supplementary vitamin E from the time of diagnosis (see Chapter 15).

Hyperkinetic Movement Disorders

Nardo Nardocci, in Handbook of Clinical Neurology, 2011

Vitamin e deficiency

Isolated vitamin E deficiency is an autosomal-recessive condition associated with a defect in the alpha-tocopherol transfer protein. It manifests with progressive ataxia, hyporeflexia, and decreased proprioceptive sensation; dystonia is infrequently reported during the disease course. However, the association of myoclonus and dystonia in one patient affected by isolated vitamin E deficiency has been reported (Angelini et al., 2002). Myoclonic dystonia was the presenting symptom and remained the only manifestation for 6 years before the appearance of typical features of the disease. Family history was negative and the child's development was normal. At age 8 years, small-amplitude head jerks began to occur during emotional stress. Two years later, torsion of the head on action and during emotional stress appeared. At age 11, the jerks worsened and were often associated with torsion of the trunk. Neurological examination disclosed irregular and arrhythmic myoclonus involving head and arms, combined with dystonic posturing of the head and slight dysarthria. Polymyography with surface electrodes disclosed features consistent with myoclonic dystonia: irregular bursts of EMG activity lasting between 100 and 250 ms, superimposed on prolonged tonic co-contraction of the trapezius and splenius muscles. Treatment with clonazepam significantly reduced the myoclonus but did not affect the dystonia. Treatment with alpha-tocopherol produced a marked reduction in dystonia, but myoclonus continued to manifest in stressful situations.

The importance of considering isolated vitamin E deficiency rests on the fact that it is eminently treatable, particularly if vitamin E supplementation is instituted promptly (Rayner et al., 1993).

The main neuropathological features of vitamin E deficiency are degeneration of large-caliber myelinated sensory axons, particularly in the posterior column, and loss of cerebellar Purkinje cells consistent with the spinocerebellar signs and symptoms observed in the condition (Yokota et al., 2000). However, pathological involvement of the nigrostriatal pathways has been described in animal models (Dexter et al., 1994b) and in vitamin E deficiency secondary to various causes, including abetalipoprotein (Dexter et al., 1994a). In these cases, the neuropathological features include nigral dopaminergic cell loss, axonal swelling in the globus pallidus and zona reticularis of the substantia nigra, reduced pigmentation of the substantia nigra, and lipofuscin-like pigment deposition in the glia of the globus pallidus, substantia nigra, and inferior putamen. These findings may explain the prominent movement disorder observed in the patient.

Manganese and Selenium

Larry R. Engelking, in Textbook of Veterinary Physiological Chemistry (Third Edition), 2015

Selenium Deficiency

Both vitamin E deficiency and Se deficiency lead to nutritional muscular degeneration (i.e., white muscle disease; see Chapter 46). Additional symptoms of Se deficiency are included in Table 51-4. Within the past few years there has been increasing interest in the role of deficiencies of specific nutritional components in the etiology of myocardial cell destruction. The most important of these appears to be the amino acid taurine (see Chapters 3 and 62), and carnitine, the compound required to shuttle long-chain fatty acids across mitochondrial membranes (see Chapter 55). Vitamin E deficiency and Se deficiency are also associated with acute myocardial necrosis in farm animals, as well as in experimental dogs. There may also be other connections between Se deficiency and cardiovascular disease. The mechanism may involve increased aggregability of platelets and production of thromboxane A2 (TXA2), with less production of prostacyclin (PGI2) from vascular endothelial cells (see Chapters 68 and 69 for more information on the functions of these eicosanoids). Heavy neonatal mortality in farm animals, chronic diarrhea in calves, infertility due to fetal resorption in ewes, and dietetic hepatosis in swine are complications that reportedly respond to dietary supplementation with this element.

Table 51-4. Selenium

Se-Deficiency SymptomsSe-Toxicity Symptoms
Growth retardation“Blind Staggers” or “Alkali
Cataract formation   Disease” in ruminant animals
Decreased spermatogenesisNeurological damage
Placental retentionRough hair
MyositisAlopecia
Muscular degenerationHoof abnormalities
CardiomyopathyGI Disorders

Lastly, the possibility that adequate Se intake may prevent or retard tumor formation indicates a need for an optimal Se intake in both humans and animals.